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Beneficial Effect of Genistein on Diabetes-Induced Brain Damage in the ob/ob Mouse Model.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-17 , DOI: 10.2147/dddt.s249608 Rong-Zi Li 1 , Xiao-Wen Ding 1 , Thangiah Geetha 1 , Layla Al-Nakkash 2 , Tom L Broderick 2 , Jeganathan Ramesh Babu 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-17 , DOI: 10.2147/dddt.s249608 Rong-Zi Li 1 , Xiao-Wen Ding 1 , Thangiah Geetha 1 , Layla Al-Nakkash 2 , Tom L Broderick 2 , Jeganathan Ramesh Babu 1
Affiliation
Purpose: Diabetes mellitus (DM)-induced brain damage is characterized by cellular, molecular and functional changes. The mechanisms include oxidative stress, neuroinflammation, reduction of neurotrophic factors, insulin resistance, excessive amyloid beta (Aβ) deposition and Tau phosphorylation. Both antidiabetic and neuroprotective effects of the phytoestrogen genistein have been reported. However, the beneficial effect of genistein in brain of the ob/ob mouse model of severe obesity and diabetes remains to be determined.
Methods: In this study, female ob/ob mice and lean control mice were fed with either a standard diet or a diet containing genistein (600mg/kg) for a period of 4 weeks. Body weight was monitored weekly. Blood was collected for the measurement of glucose, insulin and common cytokines. Mice brains were isolated for Western immunoblotting analyses.
Results: Treatment with genistein reduced weight gain of ob/ob mice and decreased hyperglycemia compared to ob/ob mice fed the standard diet. The main findings show that genistein treatment increased insulin sensitivity and the expression levels of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF). In these mice, genistein also reduced Aβ deposition and the level of hyper-phosphorylated Tau protein.
Conclusion: The results of our study indicate the beneficial effects of genistein in the obese diabetic mouse brain, including improving brain insulin signaling, increasing neurotrophic support, and alleviating Alzheimer’s disease-related pathology.
Keywords: isoflavones, leptin-deficient mice, brain injury, insulin signaling, amyloid beta
中文翻译：
在 ob/ob 小鼠模型中染料木黄酮对糖尿病引起的脑损伤的有益作用。
目的：糖尿病（DM）引起的脑损伤以细胞、分子和功能变化为特征。这些机制包括氧化应激、神经炎症、神经营养因子的减少、胰岛素抵抗、淀粉样蛋白β (Aβ) 过度沉积和 Tau 磷酸化。已经报道了植物雌激素染料木黄酮的抗糖尿病和神经保护作用。然而，染料木素在严重肥胖和糖尿病的 ob/ob 小鼠模型脑中的有益作用仍有待确定。
方法：在这项研究中，雌性 ob/ob 小鼠和瘦对照小鼠被喂食标准饮食或含有染料木黄酮 (600mg/kg) 的饮食，为期 4 周。每周监测体重。收集血液用于测量葡萄糖、胰岛素和常见细胞因子。小鼠大脑被分离用于蛋白质免疫印迹分析。
结果：与喂食标准饮食的 ob/ob 小鼠相比，用染料木黄酮治疗可减少 ob/ob 小鼠的体重增加并降低高血糖症。主要研究结果表明，染料木黄酮治疗增加了胰岛素敏感性和神经营养因子神经生长因子 (NGF) 和脑源性神经营养因子 (BDNF) 的表达水平。在这些小鼠中，染料木黄酮还减少了 Aβ 沉积和过度磷酸化 Tau 蛋白的水平。
结论：我们的研究结果表明染料木黄酮对肥胖糖尿病小鼠大脑的有益作用，包括改善大脑胰岛素信号传导、增加神经营养支持和减轻阿尔茨海默病相关的病理学。
关键词：异黄酮，瘦素缺陷小鼠，脑损伤，胰岛素信号，β淀粉样蛋白
更新日期：2020-08-17
Methods: In this study, female ob/ob mice and lean control mice were fed with either a standard diet or a diet containing genistein (600mg/kg) for a period of 4 weeks. Body weight was monitored weekly. Blood was collected for the measurement of glucose, insulin and common cytokines. Mice brains were isolated for Western immunoblotting analyses.
Results: Treatment with genistein reduced weight gain of ob/ob mice and decreased hyperglycemia compared to ob/ob mice fed the standard diet. The main findings show that genistein treatment increased insulin sensitivity and the expression levels of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF). In these mice, genistein also reduced Aβ deposition and the level of hyper-phosphorylated Tau protein.
Conclusion: The results of our study indicate the beneficial effects of genistein in the obese diabetic mouse brain, including improving brain insulin signaling, increasing neurotrophic support, and alleviating Alzheimer’s disease-related pathology.
Keywords: isoflavones, leptin-deficient mice, brain injury, insulin signaling, amyloid beta
中文翻译：
在 ob/ob 小鼠模型中染料木黄酮对糖尿病引起的脑损伤的有益作用。
目的：糖尿病（DM）引起的脑损伤以细胞、分子和功能变化为特征。这些机制包括氧化应激、神经炎症、神经营养因子的减少、胰岛素抵抗、淀粉样蛋白β (Aβ) 过度沉积和 Tau 磷酸化。已经报道了植物雌激素染料木黄酮的抗糖尿病和神经保护作用。然而，染料木素在严重肥胖和糖尿病的 ob/ob 小鼠模型脑中的有益作用仍有待确定。
方法：在这项研究中，雌性 ob/ob 小鼠和瘦对照小鼠被喂食标准饮食或含有染料木黄酮 (600mg/kg) 的饮食，为期 4 周。每周监测体重。收集血液用于测量葡萄糖、胰岛素和常见细胞因子。小鼠大脑被分离用于蛋白质免疫印迹分析。
结果：与喂食标准饮食的 ob/ob 小鼠相比，用染料木黄酮治疗可减少 ob/ob 小鼠的体重增加并降低高血糖症。主要研究结果表明，染料木黄酮治疗增加了胰岛素敏感性和神经营养因子神经生长因子 (NGF) 和脑源性神经营养因子 (BDNF) 的表达水平。在这些小鼠中，染料木黄酮还减少了 Aβ 沉积和过度磷酸化 Tau 蛋白的水平。
结论：我们的研究结果表明染料木黄酮对肥胖糖尿病小鼠大脑的有益作用，包括改善大脑胰岛素信号传导、增加神经营养支持和减轻阿尔茨海默病相关的病理学。
关键词：异黄酮，瘦素缺陷小鼠，脑损伤，胰岛素信号，β淀粉样蛋白
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